Complex biologically active molecules are challenging, expensive, and time-consuming to synthesize. Synthesizing chiral, non-racemic compounds with good enantio- and diastereoselectivity is even more challenging. Doing so generally involves isolating or synthesizing an enantioenriched intermediate whose stereochemistry can be preserved in the required subsequent synthetic transformations.
An example of a useful intermediate in the synthesis of a biologically active molecule is (1R,2R)-1-((tert-butoxycarbonyl)amino)-2-(difluoromethyl)cyclopropanecarboxylic acid (1, Boc-DFAA). In the past, this intermediate was synthesized from (1R,2S)-2 using corrosive fluorination chemistry, which is not suitable for large scale production. WO 2009/064975.

There exists a need for new synthetic methods to construct enantioenriched difluoroalkylcyclopropyl amino esters and their precursors.